Speicher im Stromsystem der Energiewende.: Eine Flexibilitätsoption im Wettbewerb

Mit dem Ausbau der erneuerbaren Energien muss auch mehr für den Ausgleich der wetterabhängigen Erzeugung aus Wind und Sonne im Stromsystem getan werden. Um den steigenden Anteil schwankender Erzeugung zu integrieren, kommen unter anderem Speicher infrage. Aber auch Maßnahmen auf der Erzeugungs- und auf der Nachfrageseite sowie der regionale Ausgleich über das Stromnetz selbst können zu einer weiteren Flexibilisierung des Energiesystems beitragen. Welche Kombination dieser Flexibilitätsoptionen sich durchsetzt, hängt von ihren Kosten, dem energiewirtschaftlichen Rahmen, aber auch von den Bedürfnissen der Kunden ab. Der Artikel skizziert, wie ein kosteneffizientes Zusammenspiel von Flexibilitätsoptionen auch ohne genaue Kenntnis ihrer zukünftigen Entwicklung möglich wird. Eine Schlüsselrolle spielt dabei die kontinuierliche Weiterentwicklung des Strommarktdesigns. Der Energiemarkt in seiner heutigen Form ermöglicht bereits in umfangreichem Maße den effizienten Einsatz bestehender Flexibilitätsalternativen. Am Beispiel von Batterien ist jedoch zu sehen, dass Preissignale des Marktes bei einigen Akteuren teilweise von weiteren Umlagen und Entgelten überlagert werden, sodass der Einsatz dieser Flexibilitätsoption derzeit unwirtschaftlich ist. Dies ist eine Erkenntnis, die auch das Bundesministerium für Wirtschaft und Energie in seinem kürzlich veröffentlichten Weißbuch „Ein Strommarkt für die Energiewende“ aufgegriffen hat und das in ersten Ansätzen aufzeigt, wie zukünftig weitere Flexibilitäten erschlossen werden sollen.Due to the development of renewable technologies it is also necessary to do more for the balancing of the weather-dependent production from wind and sun in the electricity grid. Storage units are a way to integrate the gradually growing use of fluctuating production. But also measures on the supply and demand side as well as the regional compensation through the electricity grid can contribute to an increased flexibility of the energy system. Which combination of these flexibility options will prevail depends on the costs, the energy-economic frame as well as the needs of consumers. Our contribution outlines how a cost efficient interplay of flexibility options is possible without exactly knowing their future development. A key role hereby is the continuous development of the design of the electricity market. In its current form, the energy market already enables the extensive use of existing flexibility options. Yet, as the example of batteries shows, price signals of the market are partly overlain by allocations and fees, making the use of this flexibility option uneconomic at the moment. This insight is also shared by the Federal Ministry of Economic Affairs and Energy, which just published the white paper “An electricity market for Germany’s energy transition” showing first approaches how to develop future flexibilities

SimbaML: Connecting Mechanistic Models and Machine Learning with Augmented Data

Training sophisticated machine learning (ML) models requires large datasets that are difficult or expensive to collect for many applications. If prior knowledge about system dynamics is available, mechanistic representations can be used to supplement real-world data. We present SimbaML (Simulation-Based ML), an open-source tool that unifies realistic synthetic dataset generation from ordinary differential equation-based models and the direct analysis and inclusion in ML pipelines. SimbaML conveniently enables investigating transfer learning from synthetic to real-world data, data augmentation, identifying needs for data collection, and benchmarking physics-informed ML approaches. SimbaML is available from https://pypi.org/project/simba-ml/.Comment: 6 pages, 1 figur

Liposomal formulations of mistletoe produced by centrifugal technologies and cell proliferation analysis of both mistletoe extracts and isolated mistletoe lectin I = Liposomale Formulierung von Mistelextrakten durch Zentrifugationsverfahren und Analyse der Zellproliferation von Gesamtextrakten und isoliertem Mistellektin I

Um Liposomen aus Nanoemulsionen herzustellen, wird ein Zentrifugationsverfahren entwickelt, das eine hohe Einkapselungseffizienz und asymmetrische Membranen ermöglicht. Heparin-Komplexe werden für die Bildung einer stabilen Schutzschicht verwendet. Um die Erprobung der liposomalen Formulierungen in vitro und in vivo zu ermöglichen, wurden Mistelpräparate mit unterschiedlicher Viscotoxin-(VT) und Mistellektin-(ML) Zusammensetzung sowie isoliertes ML°I an Maus-Zelllinien erprobt. Ein Proliferationstest wurde durchgeführt, um die inhibierenden Konzentrationen (IC50) zu ermitteln und sensitive Zelllinien für in vivo Experimente auszuwählen. abnobaVISCUM (AV) Pini Präparate, die den geringsten Gesamtgehalt an ML und eine Dominanz von ML III aufweisen, zeigten bei B16-F10 Melanomzellen eine stärkere Inhibierung der Proliferation im Vergleich zu den ML I reichen Präparaten AV Fraxini und Quercus. Für AV Fraxnini und AV Quercus wurde gezeigt, dass die Zytotoxizität überwiegend auf ML I zurückzuführen ist und ML I daher als potentieller Wirkstoff zur Verkapselung in Liposomen geeignet ist. Auf isoliertes ML I reagiert die getestete Kolonkarzinomzelllinie C26 deutlich empfindlicher als die aggressive B16-F10 Melanomzelllinie. Diese Ergebnisse erlauben den Vergleich eines sensitiven mit einem aggressiven Tumormodell in vivo. Im Vergleich zu C26 ist die Makrophagenzelllinie RAW264.7 relativ unempfindlich gegenüber isoliertem ML I. Die Ergebnisse deuten auf die Möglichkeit einer gezielten Therapie von z.B. Kolontumoren hin, bei der die Immunfunktionen intakt bleiben

Structures of active melanocortin-4 receptor−Gs-protein complexes with NDP-α-MSH and setmelanotide

The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is a class A G-protein-coupled receptor and a prime target for the pharmacological treatment of obesity. Here, we present cryo-electron microscopy structures of MC4R–Gs-protein complexes with two drugs recently approved by the FDA, the peptide agonists NDP-α-MSH and setmelanotide, with 2.9 Å and 2.6 Å resolution. Together with signaling data from structure-derived MC4R mutants, the complex structures reveal the agonist-induced origin of transmembrane helix (TM) 6-regulated receptor activation. The ligand-binding modes of NDP-α-MSH, a high-affinity linear variant of the endogenous agonist α-MSH, and setmelanotide, a cyclic anti-obesity drug with biased signaling toward Gq/11, underline the key role of TM3 in ligand-specific interactions and of calcium ion as a ligand-adaptable cofactor. The agonist-specific TM3 interplay subsequently impacts receptor–Gs-protein interfaces at intracellular loop 2, which also regulates the G-protein coupling profile of this promiscuous receptor. Finally, our structures reveal mechanistic details of MC4R activation/inhibition, and provide important insights into the regulation of the receptor signaling profile which will facilitate the development of tailored anti-obesity drugs

Effective nebulization of interferon-γ using a novel vibrating mesh.

BACKGROUND: Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. METHODS: Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). RESULTS: Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. CONCLUSIONS: It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations

Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition). The results showed that the efficacy of salbutamol sulfate’s aerosolization performance was, in part, due to the introduction of L-leucine in the carrier, prior to being spray-dried, accounting for an increase in the fine particle fraction (FPF) of salbutamol sulfate from spray-dried lactose-leucine (0.5% leucine) in comparison to all other carriers. It was shown that all of the spray-dried carriers were spherical in their morphology with some agglomerates and contained a mixture of amorphous, α-lactose, and β-lactose. It was also interesting to note that spray-dried lactose-leucine particles were agglomerated during the spray-drying process to make coarse particles (volume mean diameter of 79 to 87 μm) suitable as a carrier in DPI formulations

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose